Long-term Video-EEG Monitoring Findings in Children and Adolescents with Intractable Epilepsy.

Objective
Long Term Video-EEG Monitoring (LTM) may give us important information in the preoperative assessment of these patients. We performed this study for the first time in pediatric age group in Iran.


Materials and Methods
In this cross-sectional study, 43 children between 4 to 18 yr, with intractable epilepsy referred to Shefa Neuroscience Research Center, Tehran, Iranfrom2007-2012, were enrolled to study in order to evaluate their long-term video EEG findings.


Results
The patients mean age was10.07 yr, from which 24(65.9%) were boys.Seven patients with definite epileptogenic zone were advised to perform lesionectomy surgery.In two patients, there was not any seizure onset focus but corpus callosotomy was advised to control their frequent falling.Eight cases were recommended to perform electrocorticography or invasive EEG monitoring and26 cases to adjust medical treatment. In three cases, there was not any electrical seizure activity during clinical attacks, so discontinuing anti-epileptic drugs were recommended fordiagnosis of conditions that mimic epilepsy.


Conclusion
It is necessary to perform LTM in patients with refractory epilepsy in order to determine their treatment strategy. If there is any doubt about pseudoseizureLTM can help to differentiate epilepsy from conditions that mimic epilepsy.


Introduction
A seizure is a paroxysmal involuntary, time-limited change in brain function, resulting from abnormal discharges from cerebral neurons. It is called epilepsy if it occurs two times or more without any provocation (1)(2)(3). Intractable epilepsy, if untreated, can lead to cognitive decline, impaired mental and social status, lifestyle disruption and patient dependency (4). The biologic basis of seizure recurrence lies in conditions such as severe epileptic syndromes, underlying neuropathological diseases, abnormal reorganization of neurons, replacement of receptors and clinical images will be recorded for 12 h to a few days. Hence, clinical symptoms and brain waves can be studied simultaneously (12). The test is noninvasive and patient feels no pain or discomfort during hospitalization. The test allows the physician to review the patient's brain electrical activity when he/she has abnormal behaviors or seizure attacks; to determine the focus of seizure in the brain, diagnose the nature of invasive abnormalities, and select the best and most effective method of treatment (medical or surgical) (8). LTM has been very effective in patients with frequent attacks whose definite diagnosis could not be reached by conventional methods. Using LTM in patients with epilepsy, physician can monitor patient's 24 h activities, both during sleep and waking hours;to determine the type and frequency of seizures (8). Furthermore, this test helps physician to determine the focus of seizure, differentiate between nonepileptic and epileptic seizures, classify attacks, detect epileptic syndromes, determine the number of seizures and epilepsy mimicking disorders (i.e. tic disorders, sleepwalking disorders, night terrors and cataplexy) (8,9). Analyzing the results of LTM during and between attacks provides precise knowledge of brain points' function (10, 11). As LTM is a new method and due to the lack of studies in this field in Iran, for the first time in Iran, this study aimed to evaluate the long-term video-EEG findings in pediatric and young patients of 4 to 18 yr with refractory epilepsy.

Materials and Methods
This cross-sectional study was conducted from 2007 to 2012, on all pediatric and young patients of 4 to 18 yr referred to Shefa Neuroscience Research Center, Tehran, Iran. They were diagnosed with refractory epilepsy. Inclusion criteria included having a medical diagnosis of refractory epilepsy made by a specialist in Pediatric Neurology and not having a history of surgery for epilepsy.Using a consecutive sampling method, all the 43 patients with refractory epilepsy were recruited in the study. Ethics permissions for the study were obtained from the hospital authorities and an informed consent was signed by parents of patients. Data collection instrument consisted of two parts. The neurotransmitters, ion channel disorders, reactive autoimmune disorders, and improper use of anti-epileptic drugs (4). Epileptic seizures may occur due to exposure to bright lights, video games, repetitive sounds, sleep deprivation, excessive alcohol consumption, stress, smoking and hormonal changes (5). The annual incidence of epilepsy is 0.5%-0.8%and cumulative incidence is about 3% during lifetime; more than half of the cases occur in childhood (1). A seizure is resolved in 60%-70% of children with epilepsy after a year or two with medications. However, its attacks continue in 10%-20% of children despite receiving appropriate medications (2). Failure in initial treatment with antiepileptic drugs may be due to inappropriate drugs dosages, ineffectiveness of the type medications, or drug intolerance (4). Medical treatment is effective and the primary method of epilepsy treatment depends on a number of factors including patient's age, type of epilepsy, drug interactions, ease of use and side effects of medications. Depending on the type and number of seizures, patient's condition or the underlying cause, some nonpharmacologic treatments such as brain surgery, vagus nerve stimulation, or ketogenic diet might be used in specific cases, where patient does not respond to medical treatment and his or her normal life is disrupted (6). Despite similar seizure disorders or similar lesions on MRI, patients with epilepsy respond differently to treatment and some are resistant or refractory to all available treatments (1). A refractory seizure or refractory epilepsy is defined as seizure activity, which occurs at least once a month for at least two years, despite treatment with three antiepileptic drugs (7). Patients' medical history, seizure semiology, and electroencephalogram (EEG) are usually used for diagnosis. Long-term electroencephalography or video-EEG help to identify abnormal brain waves (6). In some patients with refractory epilepsy, the focus of seizure can be diagnosed by brain CT scan or MRI. However, in some patients, there are microscopic abnormalities diagnosed by Long-term Video-EEG Monitoring (LTM) (8). LTM is a specialized form of EEG performed by continuous monitoring of brain activity and video recording of clinical behavior. To perform the LTM, the patient will be hospitalized and his brain waves and epileptogenic zone. Moreover, four patients (9.30%) had normal Interictal EEG and 39 patients (90.69%) had abnormal interictal EEG. Table 3 shows the relationship between interictal EEG and seizure type and epileptogenic zone. There wasno significant relationship between seizure type and focus and EEG findings( Table 2 and 3). There wassignificant relationship between type and number of attacks (P=0.047) ( Table 4). Moreover, no significant relationship was found between ictal and interictal EEG findings and brain MRI findings (P=0.579 and P=0.436) ( Table 5). However, a significant relationship was found between resultsof brain MRI and the type of treatment (P=0.005). Nonetheless, nosignificant relationship was found between ictal and interictal EEG findings and the type of treatment (Table 6). Table 7 shows the final medical recommendations prescribed after reviewing the results of LTM and the dedicated brain MRI in 43 patients. First group: Nine patients were recommended having surgery; seven patients (77.7%) had a localized seizure focus were recommended to have lesionectomy surgery. Two patients (22.3%) had no seizure focus but they were recommended to have Corpus callosotomy surgery to prevent frequent falling due to frequent seizures. Second group: Eight patients were recommended electrocorticography or invasive EEG monitoring to determine the seizure focus precisely. Third group: 26 patients were recommended to continue but reform medical treatments. Seizure focuses of two patients (8%) were well defined but they were recommended to continue pharmacological treatment because it was at frontotemporal area and there were high risks for motor cortical damaged during surgery. Attacks of three patients were seizure imitators (11.5%), therefore they were recommended to discontinue treatment. One of these patients had hemifacial spasms, one had autism spectrum disorder and one had a nonepileptic attack recommended seeking psychiatric consultation (Table 8).

Discussion
LTM is a specialized form of brain EEG done as continuous and long-term monitoring of brain activity and video recording of clinical behavior. It leads first part included questions on the patient's age, sex, date of the first seizure, the number of seizures in 2 yr, drugs used so far (three drugs or less) and type of seizure (generalized, partial, mixed). The second part of the data collection instrument included items on EEG findings during the attack (ictal EEG), EEG findings between attacks (interictal EEG), location of the seizure focus, brain MRI information, and the LTM data. The needed data were gathered from the patients' hospital flies or through clinical observations and interviews with parents. LTM and behavioral observationswere performed on all patients for several hours to several days. In each case, the LTM was stopped and the results were recorded after two or more clinical seizures. Statistical analysis was carried out using SPSS software version 17(Chicago, IL, USA).Kolmogorov-Smirnov test was performed to examine the normality of the data. Then, Mann-Whitney U, analysis of variance (ANOVA) and Fisher's exact tests were used to investigate the relationship between variables. Statistical significance was considered at P-value <0.05.

Results
Totally, 43 patients including 24 boys (55.82%) and 19 girls (44.18%) were enrolled in this study. The mean age of boys and girls was8.7 ± 12 and 11.13 ± 8 yr, respectively.Twenty-four people (55.82 %) had partial seizures, while 11 (25.58%) and eightcases(18.6%) had generalized or mixed type seizures, respectively. No significant relationship was found between patients' age and type of seizure (P=0.790) ( Table 1). Regarding theclinical semiology of seizure attacks, 53.4% (n= 23) of attacks were focal motor, followed by generalized motor (n= 12, 27.9%), myoclonic (n= 10, 23.2%), dialeptic (n= 9, 20.9%), visual aura (n=3, 6.9%), auto motor (n= 2, 4.6%), oral motor (n= 2, 4.6%), atonic (n= 2, 4.6%), hyper motor (n= 2, 4.6%), jelastic (n= 1, 2.3%), epigastric pain aura (n= 1, 2.3%), and nonepileptic attacks (n= 1, 2.3%) (Figure1). Findings of electroencephalography and Brain MRI were as follows: Five patients (11.63%) had normal Ictal EEG while 38 cases(88.37%) had abnormal Ictal EEG. Table 2 shows the relationship between Ictal EEG and seizure type and physicians to select the best and most effective way of treatment for patients with refractory epilepsy (8). Using LTM and Brain MRI we could correctly diagnose the focus of epilepsy in 20 (46.51%) of 43 pediatric patients with refractory epilepsy. Using LTM, 60 patients were studied with 10 yr of epilepsy. Then, 40% of patients were diagnosed as having pseudoseizures. Therefore, they strongly recommended that LTM is used in diagnosis of symptomatic seizures (13). The effect of LTM was examined before surgery in 56patients with refractory epilepsy. LTM can detect about 90% of seizure types (9). In this study, the power of LTM in diagnosing the type of seizure was confirmed and 55.8% of seizures were partial and 25.5% were generalized while 6.9% of patients had pseudoseizures. The low incidence of pseudoseizures in pediatric group seems reasonable. In this study, 6.9% of patients were diagnosed as pseudoseizures and were referred to discontinue drugs. Moreover, eight patients (19.7%) were referred for invasive monitoring. In a study, 454 patients in age range of 11 d to 20 yr were studied using LTM. Totally, 23.6%and 24.9%of patients were diagnosed as generalized or partial seizures respectively; while 35% had pseudoseizures that were recommended to discontinue antiepileptic drugs and nine cases (2%) were referred for invasive monitoring (14). In the current study, among three patients (6.9%) with pseudo seizures, one patient consumed more than three antiepileptic drugs and two cases consumed three antiepileptic drugs. In a study, 33 (18%) out of 182 patients with refractory epilepsy had pseudo seizures and consumed more than 1.5 antiepileptic and 1.5 psychiatric medications (15). In Conclusion, as a non-invasive diagnostic method, LTM is very useful not only in diagnosing and differentiating the type of seizures (false or true); however, in localizing the seizure focus in children with refractory epilepsy. Therefore, facilities for LTM are created at all specialized centers of epilepsy. Then, the quality of diagnosis and treatment of refractory epilepsy and consequently the quality of life of patients would be improved.

Author`s Contribution
Y. Ghazavi: substantial contributions to the conception and drafting the work E.Aayesh Zarchi: Acquisition, analysis T.Taheri: neurosurgery consultation M.Safiabadi: Acquisition and analysis of dataand interpretation of data for the work .E.Rahimian: MRI interpretation and neuroradiologic consultation S.Amirsalari: Clinical diagnosis, patient selection for LTM, EEG interpretation and final decisions All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.